This proposal is for investigation of the kinetics of transcorneal flux and intra-ocular fate of pilocarpine. Methods and mechanisms of flux enchancement is of special interest. Central to these studies is use of a transport chamber to test drug transport across the rabbit cornea in a closed system under simulated physiological conditions. Previous work with this chamber system has shown that pilocarpine flux efficiency is inversely related both to loading dose and retention (depot), or apparant retention, of drug within the conea. The depot effect and transcorneal flux inhibition are both significantly reduced by the mediation of various hydrogel polymer vehicles. The peliminary studies suggest that topically administered drugs of low lipid solubility are transported into the internal eye mainly by slow diffusion, but also by another mechanism which is more efficient than governing high dose flux. This other mechanism is mobilized by hydrogel mediated delivery. The mechanism is both saturable and probably inhibited by high drug doses in the pharmacologic range. Proposed investigations are designed to determine the anatomical site and kinetics of flux inhibition, and the therapeutic significance of apparant intracorneal pilocarpine retention (or degradation) as a potential drug "reservoir" for continuing cholinergic effect. The relation of apparent retention to the mechanism of hydrogel mediated flux enhancement may be clarified. Vehicle mediated transcorneal penetration kinetics of carbachol are being investigated to test if flux characteristics of pilocarpine are applicable to other drugs, and also to investigate carbachol as a possible competitive inhibitor of carrier mediated low dose pilocarpin flux. The potential of carbachol flux enhancement by hydrogel polymers will be evaluated at the same time.